Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and ß-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.
In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.
We successfully developed an enantioselective trifluoromethylthiolation of structurally diverse carbonyl compounds. Trichloroisocyanuric acid and AgSCF3 were employed to generate active electrophilic trifluoromethylthio species in situ for asymmetric C-SCF3 bond formation. A broad variety of chiral SCF3-carbon nucleophiles (pyrazolones, ß-keto esters, and ß-keto amides) were obtained in excellent yields with high enantioselectivities (up to 92% ee) by Cinchona alkaloid derived squaramide catalysts. The reaction exhibits high efficiency, good enantioselectivity, and high functional group tolerance, which provided a novel and efficient way for asymmetric synthesis of trifluoromethylthiolated carbonyl compounds.
Intronic polyadenylation (IPA) refers to a particular type of alternative polyadenylation where a gene makes use of a polyadenylation site located within its introns. Aberrant IPA events have been observed in various types of cancer. IPA can produce noncoding transcripts or truncated protein-coding transcripts with altered coding sequences in the resulting protein product. Therefore, IPA events hold the potential to act as a reservoir of tumor neoantigens. Here, we developed a computational method termed DIPAN, which incorporates IPA detection, protein fragmentation, and MHC binding prediction to predict IPA-derived neoantigens. Utilizing RNA-seq from breast cancer cell lines and ovarian cancer clinical samples, we demonstrated the significant contribution of IPA events to the neoantigen repertoire. Through mass spectrometry immunopeptidome analysis, we further illustrated the processing and presentation of IPA-derived neoantigens on the surface of cancer cells. While most IPA-derived neoantigens are sample-specific, shared neoantigens were identified in both cancer cell lines and clinical samples. Furthermore, we demonstrated an association between IPA-derived neoantigen burden and overall survival in cancer patients.
Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.
Transition-metal dichalcogenides (TMDCs), as emerging optoelectronic materials, necessitate the establishment of an experimentally viable system to study their interaction with light. In this study, we propose and analyze a WS2/PMMA/Ag planar Fabry-Perot (F-P) cavity, enabling the direct experimental measurement of WS2 absorbance. By optimizing the structure, the absorbance of A exciton of WS2 up to 0.546 can be experimentally achieved, which matches well with the theoretical calculations. Through temperature and thermal expansion strain induced by temperature, the absorbance of the A exciton can be tuned in situ. Furthermore, temperature-dependent photocurrent measurements confirmed the consistent absorbance of the A exciton under varying temperatures. This WS2/PMMA/Ag planar structure provides a straightforward and practical platform for investigating light interaction in TMDCs, laying a solid foundation for future developments of TMDC-based optoelectronic devices.
Amorphous ethylene-cyclic olefin copolymers (COCs) which can be used in cell phone lenses and prefilled syringes have attracted increasing attention due to their excellent and tunable thermal properties. In order to better explain the influence of COC microstructure (cyclic olefin types and content) on the glass transition mechanism, we used molecular dynamics (MD) simulations to track the evolution of free volume, diffusion coefficients, atomic mobility, trans conformation probabilities, and characteristic parameters of α-relaxation kinetics during the quenching process. MD results show that for the classic COC E-co-NB (ethylene-norbornene copolymer), an increase in cyclic olefin content from 25 to 50 mol % reduces atomic mobility, limiting the molecular chain movement at higher temperatures and improving Tg. Compared to NB, the more rigid rings in tricyclopentadiene (TCPD) and exo-1,4,4a,9,9a,10-hexahydro-9,10(1',2')-bridged phenylidene-1,4-bridged methylideneanthracene (HBM) have the following effects: (1) reducing the thermal expansion coefficient and overall chain mobility; (2) enhancing the diffusion energy barrier; (3) promoting the formation of local ordered structures; (4) accelerating α-relaxation dynamics at high temperatures and improving the dynamic fragility m. These lead to an upward shift in the temperature region where chain movement is limited and thus improve Tg and high-temperature dimensional stability. In this simulation, the correlation equation between Tg, m, and the microstructural parameters of COCs is established, which is of great significance for the development of COCs with high performance.
316L stainless steel pipes are widely used in the storage and transportation of low-temperature media due to their excellent low-temperature mechanical properties and corrosion resistance. However, due to their low thermal conductivity and large coefficient of linear expansion, they often lead to significant welding residual tensile stress and thermal cracks in the weld seam. This also poses many challenges for their secure and reliable applications. In order to effectively control the crack defects caused by stress concentration near the heat-affected zone of the weld, this paper establishes a thermal elastoplastic three-dimensional finite element (FE) model, constructs a welding heat source, and simulates and studies the influence of process parameters on the residual stress around the pipeline circumference and axial direction in the heat-affected zone. Comparison and verification were conducted using simulation and experimental methods, respectively, proving the rationality of the finite element model establishment. The axial and circumferential residual stress distribution obtained by the simulation method did not have an average deviation of more than 30 MPa from the numerical values obtained by the experimental method. This study also considers the effects of welding energy, welding speed, and welding start position on the pipe's circumferential and axial residual stress laws. The results indicate that changes in welding energy and welding speed have almost no effect on the longitudinal residual stress but have a more significant effect on the transverse residual stress. The maximum transverse residual stress is reached at a welding energy of 1007.4~859.3 J/mm and a welding speed of 6.6 mm/s. Various interlayer arc-striking deflection angles can impact the cyclic phase angle of the transverse residual stress distribution in the seam center, but they do not alter its cyclic pattern. They do influence the amplitude and distribution of the longitudinal residual stress along the circumference. The residual stress distribution on the surface of the pipe fitting is homogenized and improved at 120°.
BACKGROUND: Renal mTORc2 plays a role in regulating renal K+-excretion (renal-EK) and K+-homeostasis. Inhibition of renal mTORc2 caused hyperkalemia due to suppressing epithelial-Na+-channel (ENaC) and ROMK (Kir1.1) in the collecting duct. We now explore whether mTORc2 of DCT regulates basolateral Kir4.1/Kir5.1, NCC and renal-EK. METHODS: We used patch-clamp-technique to examine basolateral Kir4.1/Kir5.1 in early-DCT, immunoblotting and immunofluorescence to examine NCC expression and in vivo measurement of urinary K+-excretion to determine baseline renal-EK in the mice treated with mTORc2-inhibitor and in DCT-specific Rapamycin-Insensitive-Companion- of-mTOR knockout (DCT-RICTOR-KO) mice. RESULTS: Inhibition of mTORc2 with AZD8055 abolished high-K+-induced inhibition of Kir4.1/Kir5.1 in DCT, high-K+-induced depolarization of DCT membrane and high-K+-induced suppression of pNCC expression. AZD8055 stimulated the 40-pS-inwardly-rectifying-K+ channel (Kir4.1/Kir5.1-heterotetramer) in early-DCT in the mice on overnight-high-K+, this effect was absent in the presence of PKC-inhibitor which also stimulated Kir4.1/Kir5.1. AZD8055-treatment decreased renal-EK in animals on overnight-high-K+. Deletion of RICTOR in the DCT increased the Kir4.1/Kir5.1-mediated K+-currents, hyperpolarized DCT membrane and increased the expression of pWNK4 and pNCC. Renal-EK was lower and plasma-K+ was higher in DCT-RICTOR-KO mice than corresponding control mice. Also, overnight-high-K+ did not inhibit Kir4.1/Kir5.1 activity in the DCT and failed to inhibit the expression of pNCC in DCT-RICTOR-KO mice. Overnight-high-K+ stimulated renal-EK in control mice, but this effect was attenuated in DCT-RICTOR-KO mice. Thus, overnight-high-K+ induced hyperkalemia in DCT-RICTOR-KO mice but not in control mice. CONCLUSIONS: mTORc2 of the DCT inhibits Kir4.1/Kir5.1 activity and NCC expression, and stimulates renal-EK during high-K+-intake.
The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.
ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor-suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well-explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. AIM OF THE STUDY: Tumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. MATERIALS AND METHODS: Through in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor-associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity-related axis. RESULTS: Xihuang Pill has a regulatory effect on the tumor immune microenvironment. CONCLUSIONS: The results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL-6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein.
B7-H1 Antigen , Drugs, Chinese Herbal , Liver Neoplasms , STAT3 Transcription Factor , Tumor Microenvironment , Tumor Microenvironment/drug effects , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Animals , STAT3 Transcription Factor/metabolism , B7-H1 Antigen/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Mice , Humans , Signal Transduction/drug effects , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/immunology , Male , Cell Line, Tumor , Mice, Inbred BALB C , Mice, Inbred C57BL
OBJECTIVE: To evaluate the effects of argatroban on the levels of Hcy, hs-CRP and FIB in patients with acute cerebral infarction (ACI). METHODS: A retrospective analysis was performed on 382 patients with ACI who were hospitalized in the Department of Neurology of our hospital from January 2017 to December 2019. Among them, 158 patients received conventional treatment as the control group and 224 patients received combined treatment with argatroban as the study group. NHISS score, mRS score, Hcy, hs-CRP, FIB level, quality of life, adverse reactions were compared between the two groups after treatment. The levels of Hcy and hs-CRP in patients with different mRS scores were compared. RESULTS: A superior clinical efficacy of the study group was observed than the control group (p < 0.05). The study group witnessed a remarkably lower NHISS score, Hcy, hs-CRP and FIB level as compare to the control group (p < 0.05). The ADL and FMA scores in the study group were higher than those in the control group (p < 0.05). The levels of Hcy and hs-CRP in mRS 0-2 patients were lower than those in mRS 3-6 patients (p < 0.05). CONCLUSION: Argatroban in ACI patients can significantly enhance the clinical efficacy and improve the quality of life. It is closely related to the reduction of Hcy and hs-CRP levels, but the mechanism needs to be further studied.
Hydrogen peroxide (H2O2) and ascorbic acid (AA), acting as two significant indicative species, correlate with the oxidative stress status in living brains, which have historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease (PD). The development of efficient biosensors for the simultaneous measurement of their levels in living brains is vital to understand their roles played in the brain and their interactive relationship in the progress of these diseases. Herein, a robust ratiometric electrochemical microsensor was rationally designed to realize the determination of H2O2 and AA simultaneously. Therefore, a specific probe was designed and synthesized with both recognition units responsible for reacting with H2O2 to produce a detectable signal on the microsensor and linkage units helping the probe modify onto the carbon substrate. A topping ingredient, single-walled carbon nanotubes (SWCNTs) was added on the surface of the electrode, with the purpose of not only facilitating the oxidation of AA but also absorbing methylene blue (MB), prompting to read out the inner reference signal. This proposed electrochemical microsensor exhibited a robust ability to real-time track H2O2 and AA in linear ranges of 0.5-900 and 10-1000 µM with high selectivity and accuracy, respectively. Eventually, the efficient electrochemical microsensor was successfully applied to the simultaneous measurement of H2O2 and AA in the rat brain, followed by microinjection, and in the PD mouse brain.
Ascorbic Acid , Brain , Electrochemical Techniques , Hydrogen Peroxide , Nanotubes, Carbon , Hydrogen Peroxide/analysis , Ascorbic Acid/analysis , Animals , Mice , Brain/metabolism , Nanotubes, Carbon/chemistry , Biosensing Techniques , Electrodes
The enterovirus A71 (EV71) inactivated vaccine is an effective intervention to control the spread of the virus and prevent EV71-associated hand, foot, and mouth disease (HFMD). It is widely administered to infants and children in China. The empty particles (EPs) and full particles (FPs) generated during production have different antigenic and immunogenic properties. However, the antigen detection methods currently used were established without considering the differences in antigenicity between EPs and FPs. There is also a lack of other effective analytical methods for detecting the different particle forms, which hinders the consistency between batches of products. In this study, we analyzed the application of sedimentation velocity analytical ultracentrifugation (SV-AUC) in characterizing the EPs and FPs of EV71. Our results showed that the proportions of the two forms could be quantified simultaneously by SV-AUC. We also determined the repeatability and accuracy of this method and found that both parameters were satisfactory. We assessed SV-AUC for bulk vaccine quality control, and our findings indicated that SV-AUC can be used effectively to analyze the percentage of EPs and FPs and monitor the consistency of the process to ensure the quality of the vaccine.
Enterovirus A, Human , Ultracentrifugation , Enterovirus A, Human/immunology , Enterovirus A, Human/isolation & purification , Ultracentrifugation/methods , Humans , Viral Vaccines/immunology , Vaccines, Inactivated/immunology , Virion/immunology , Virion/isolation & purification , Hand, Foot and Mouth Disease/virology , Hand, Foot and Mouth Disease/prevention & control , China , Quality Control
Achieving visible-light photochromism is a long-term goal of chemists keen to exploit the opportunities of molecular photoswitches in multi-disciplinary research studies. Triplet-sensitization offers a flexible approach to building diverse visible-light photoswitches using existing photochromic scaffolds, circumventing the need for sophisticated molecular design and synthesis. Unfortunately, distance-dependence and environment-sensitivity of triplet-excited species remain as key challenges that severely impair sensitization efficiency and limit their practical availability. We present herein a nature-inspired nanoconfinement strategy in which a triplet-sensitized visible-light photoswitch/sensitizer system is assembled into nanoconfined micelles (d â¼ 40 nm). A ca. 10-fold efficiency increase of triplet-triplet energy transfer for photochromism as well as an amplified fluorescence on/off contrast upon bi-directional visible-light excitation (470/560 nm) was achieved in full aqueous media. By virtue of this, the hybrid photoswitchable system is successfully applied for both flash information encryption and multiple dynamic cell imaging assays, further proving its versatility in materials and life science.
BACKGROUND: Bactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology . RESULTS: The ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth. CONCLUSIONS: Generally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.
Abomasum , Camelus , Animals , Camelus/anatomy & histology , Camelus/embryology , Female , Lymphoid Tissue/anatomy & histology , Lymphoid Tissue/growth & development , Fetus , Pregnancy
Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.
Endometrial cancer (EC), the second most common malignancy in the female reproductive system, has garnered increasing attention for its genomic heterogeneity, but understanding of its metabolic characteristics is still poor. We explored metabolic dysfunctions in EC through a comprehensive multi-omics analysis (RNA-seq datasets from The Cancer Genome Atlas [TCGA], Cancer Cell Line Encyclopedia [CCLE], and GEO datasets; the Clinical Proteomic Tumor Analysis Consortium [CPTAC] proteomics; CCLE metabolomics) to develop useful molecular targets for precision therapy. Unsupervised consensus clustering was performed to categorize EC patients into three metabolism-pathway-based subgroups (MPSs). These MPS subgroups had distinct clinical prognoses, transcriptomic and genomic alterations, immune microenvironment landscape, and unique patterns of chemotherapy sensitivity. Moreover, the MPS2 subgroup had a better response to immunotherapy. Finally, three machine learning algorithms (LASSO, random forest, and stepwise multivariate Cox regression) were used for developing a prognostic metagene signature based on metabolic molecules. Thus, a 13-hub gene-based classifier was constructed to predict patients' MPS subtypes, offering a more accessible and practical approach. This metabolism-based classification system can enhance prognostic predictions and guide clinical strategies for immunotherapy and metabolism-targeted therapy in EC.
Depending on the source of the blastophore, there are various subtypes of laryngeal cancer, each with a unique metastatic risk and prognosis. The forecasting of their prognosis is a pressing issue that needs to be resolved. This study comprised 5953 patients with glottic carcinoma and 4465 individuals with non-glottic type (supraglottic and subglottic). Five clinicopathological characteristics of glottic and non-glottic carcinoma were screened using univariate and multivariate regression for CoxPH (Cox proportional hazards); for other models, 10 (glottic) and 11 (non-glottic) clinicopathological characteristics were selected using least absolute shrinkage and selection operator (LASSO) regression analysis, respectively; the corresponding survival models were established; and the best model was evaluated. We discovered that RSF (Random survival forest) was a superior model for both glottic and non-glottic carcinoma, with a projected concordance index (C-index) of 0.687 for glottic and 0.657 for non-glottic, respectively. The integrated Brier score (IBS) of their 1-year, 3-year, and 5-year time points is, respectively, 0.116, 0.182, 0.195 (glottic), and 0.130, 0.215, 0.220 (non-glottic), demonstrating the model's effective correction. We represented significant variables in a Shapley Additive Explanations (SHAP) plot. The two models are then combined to predict the prognosis for two distinct individuals, which has some effectiveness in predicting prognosis. For our investigation, we established separate models for glottic carcinoma and non-glottic carcinoma that were most effective at predicting survival. RSF is used to evaluate both glottic and non-glottic cancer, and it has a considerable impact on patient prognosis and risk factor prediction.
Carcinoma , Laryngeal Neoplasms , Humans , Prognosis , Laryngeal Neoplasms/pathology , Risk Factors , Regression Analysis
